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Study Investigating the Effect of Drugs Used to Treat Osteoporosis on the Progression of Calcific Aortic Stenosis. (SALTIRE II)

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ClinicalTrials.gov Identifier: NCT02132026
Recruitment Status : Unknown
Verified December 2014 by University of Edinburgh.
Recruitment status was:  Recruiting
First Posted : May 6, 2014
Last Update Posted : December 3, 2014
Sponsor:
Collaborator:
NHS Lothian
Information provided by (Responsible Party):
University of Edinburgh

Brief Summary:

Aortic stenosis is a condition whereby one of the heart valves (aortic valve) becomes narrowed, due to calcium deposition, over time. This can lead to chest pain, heart failure and sudden death. It is the commonest valve disease requiring surgery in the developed world and as the population becomes increasingly older, it is predicted that the prevalence of aortic stenosis will double in the next 20 years. Currently the only treatment is replacement of the aortic valve. Whilst this is excellent treatment, not everyone is suitable for it.

The primary objective of our study is to determine whether 2 drugs used in the treatment of osteoporosis (a condition of bone thinning) can halt/retard the progression of aortic stenosis. This is on the basis that studies have suggested that altered regulation of calcium metabolism may be an important mechanism perpetuating the disease. Both drugs work by reducing calcium release into the bloodstream from bones and therefore calcification of the aortic valve.

150 patients will therefore be randomly allocated to either of the trial drugs which are denosumab,the bisphosphonate (alendronic acid), or a placebo.

Positron Emission Tomography (PET) scanning is a technique where biochemically active molecules are injected and are taken up at sites of ongoing calcification activity where they emit radiation and can be detected by the PET scanner. We have previously shown that this technique can demonstrate areas of newly developing calcification on an aortic valve.

We therefore propose that patients receiving bisphosphonates or denosumab will have reduced evidence of active calcification and slower progression of their disease at two years as assessed by Echocardiography (ultrasound) and a change in their calcium score (quantity of calcium on the aortic valve measured using Computed Tomography [CT] ).

The data from this study will then be used to design a larger trial.


Condition or disease Intervention/treatment Phase
Calcific Aortic Stenosis Drug: Denosumab Drug: Alendronic Acid Drug: Denosumab Placebo Drug: Alendronic Acid Placebo Phase 2

  Show Detailed Description

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 150 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: SALTIRE II and RANKL Inhibition in Aortic Stenosis
Study Start Date : November 2014
Estimated Primary Completion Date : August 2017
Estimated Study Completion Date : August 2017


Arm Intervention/treatment
Active Comparator: Alendronic Acid
50 patients will receive once weekly Alendronic Acid tablets (70mg).
Drug: Alendronic Acid
Other Names:
  • Marketing Authorisation Number PL 30306/0032
  • ATC codes M05B A04

Placebo Comparator: Alendronic Acid placebo
25 patients will receive alendronic acid placebo tablets.
Drug: Alendronic Acid Placebo
Inert Capsule containing lactose monohydrate manufactured and labelled by Investigational Supplies Group (ISG) University of Edinburgh.

Active Comparator: Denosumab
50 patients will receive 6 monthly denosumab injections
Drug: Denosumab
Other Names:
  • Prolia
  • Marketing Authorisation Number : EU/1/11/703/003
  • ATC number M05BX04

Placebo Comparator: Denosumab Placebo
25 patients will receive a 6 monthly placebo injection.
Drug: Denosumab Placebo
subcutaneous injection of 0.9%Saline at baseline, 6 months, 12 months and 18 months




Primary Outcome Measures :
  1. Change in aortic valve calcium score [ Time Frame: Measured at Baseline, 6 months and 2 years ]
    The change in calcium score will be assessed using computed tomography and is an assessment of disease severity.


Secondary Outcome Measures :
  1. Change in aortic valve 18F-NaF uptake [ Time Frame: Measured at baseline and 6 months ]
    This is determined by positron emission tomography and is a measure of calcification activity.

  2. Change in aortic-jet velocity [ Time Frame: Measured at baseline, 6, 12, 18 and 24 months ]
    This will be determined by Doppler echocardiography and is a measure of disease severity.

  3. Change in thoracic aortic and coronary artery calcium score [ Time Frame: Measured at baseline and 2 years ]
    This will be determined by computed tomography and is an additional assessment of vascular calcification.

  4. Change in thoracic spine bone mineral density [ Time Frame: Measured at baseline and 2 years ]
    This will be determined by quantitative computed tomography.

  5. Change in quality of life determined by Short Form 36 Questionnaire [ Time Frame: Measured at baseline and 2 years ]
    Questionnaire



Information from the National Library of Medicine

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Ages Eligible for Study:   50 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. age >50 years
  2. peak aortic jet velocity of >2.5 m/s on Doppler echocardiography
  3. grade 2-4 calcification of the aortic valve on echocardiography

Exclusion Criteria:

  1. Anticipated or planned aortic valve surgery in the next 6 months,
  2. Life expectancy <2 years,
  3. Inability to undergo scanning
  4. Treatment for osteoporosis with bisphosphonates or denosumab.
  5. Long-term corticosteroid use.
  6. Abnormalities of the oesophagus or conditions which delay oesophageal/gastric emptying,

8) Inability to sit or stand for at least 30 minutes, 9) Known allergy or intolerance to alendronate or denosumab, or any of their excipients, 10) Hypocalcaemia, 11) Maintenance calcium supplementation, 12) Dental extraction within 6 months, 13) History of osteonecrosis of the jaw, 14) Major or untreated cancers, 15) Poor dental hygiene, 16) Women of child-bearing potential who have experienced menarche, are pre-menopausal, have not been sterilised or who are currently pregnant, 17) Women who are breastfeeding, 18) Renal failure (estimated glomerular filtration rate of <30 mL/min), 19) Allergy or contraindication to iodinated contrast, 20) Inability or unwilling to give informed consent, 21) Likelihood of non-compliance to treatment allocation or study protocol


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02132026


Contacts
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Contact: Tania A Pawade, MbChB 07805 306 564 tania.pawade@ed.ac.uk
Contact: Marc Dweck, MbChB, Phd marcdweck@hotmail.com

Locations
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United Kingdom
Clinical Research Facility University of Edinburgh Recruiting
Edinburgh, United Kingdom, EH16 4SA
Sponsors and Collaborators
University of Edinburgh
NHS Lothian
Investigators
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Principal Investigator: Tania A Pawade, MbChB University of Edinburgh
Study Chair: David Newby, Ba BSc PhD BM DM FRCP DSc FRSE University of Edinburgh
Principal Investigator: Dweck Marc, MbChb, Phd University of Edinburgh

Publications:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: University of Edinburgh
ClinicalTrials.gov Identifier: NCT02132026     History of Changes
Other Study ID Numbers: SALTIRE2-2014
First Posted: May 6, 2014    Key Record Dates
Last Update Posted: December 3, 2014
Last Verified: December 2014
Keywords provided by University of Edinburgh:
Aortic Stenosis
Denosumab
Alendronic Acid
Osteoporosis
Additional relevant MeSH terms:
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Aortic Valve Stenosis
Calcinosis
Constriction, Pathologic
Pathological Conditions, Anatomical
Metabolic Diseases
Heart Valve Diseases
Heart Diseases
Cardiovascular Diseases
Ventricular Outflow Obstruction
Calcium Metabolism Disorders
Denosumab
Alendronate
Bone Density Conservation Agents
Physiological Effects of Drugs